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Biomedical subjects

M Johnson

Publications and source records attributed to M Johnson.

At least 379 records · Page 21Linked to original sources

Exosites: their current status, and their relevance to the duration of action of long-acting beta 2-adrenoceptor agonists.

The four beta 2-adrenoceptor agonists, clenbuterol, bambuterol, formoterol and salmeterol, are all long-acting bronchodilators, that have distinct mechanisms for their extended durations of action. Various theories have been put forward in an attempt to explain these mechanisms. In this respect, there is strong evidence for the existence of specific additional binding sites (exosites) for salmeterol and related compounds, and that exosites exist on non-ligand recognition regions of the beta 2-adrenoceptor protein. Here, Robert Coleman and colleagues compare and contrast the profiles of action of these long-acting beta 2-adrenoceptor agonists, particularly as they relate to the role of exosites.

Adrenergic alpha-Agonists↗

Effects of three larvicides on the production of Aedes albopictus based on removal of pupal exuviae.

The production of adult Aedes albopictus from tires in northcentral Florida was monitored for 169 days by the daily removal of pupal exuviae. More than twice as many adults emerged from tires located in the shade (1.74 adults/tire/day) compared to tires in the sun (0.64 adults/tire/day). The effect of 3 larvicides on the production of adult Ae albopictus was evaluated. The fungal pathogen Lagenidium giganteum was ineffective. A liquid formulation of Bacillus thuringiensis israelensis (Acrobe) provided significant control for 47 days, whereas a slow-release pellet formulation of the insect growth regulator methoprene (Altosid) provided almost complete control for 116 days.

Aedes↗

Nurses' perceptions of urinary catheter selection and management.

Nurses are often responsible for the initiation of catherization procedures for patients within the hospital or community setting. This nursing role requires contemporary information on catheter selection and problem solving in the maintenance of urinary catheters. A descriptive survey with a questionnaire sent to registered and enrolled nurses (N = 709) within an Australian metropolitan area health service was undertaken to determine their current knowledge level in relation to catheter care practices. Registered nurses represented 91% of the sample, with 66% of the entire sample having 7 or more years of nursing experience. Only 14% of nurses believed that their knowledge levels were adequate, with very few receiving postregistration education. Only 31% of the respondents recommended the use of purely silicone catheters, these being the least cytotoxic to the urethra for longterm use. Less than half of the respondents were unaware of the availability of female-length catheters. There was a general lack of knowledge of current catheter costs that would have major implications for unit budgets. The apparent gaps in nursing knowledge of catheter care suggest the need for urgent educational programs on catheter care practices for nurses within this service and the initiation of an area-wide standardized policy in catheter selection and management.

Attitude of Health Personnel↗

The role of the cholinergic system in the development of the human cerebellum.

High affinity (-)nicotine ([3H]nicotine), alpha-bungarotoxin ([125I]alpha-bungarotoxin) and muscarinic binding ([3H]N-methyl scopolamine) in the human cerebellum were compared between the foetal period (23-39 weeks gestation) and young adulthood (14-34 years) in an autoradiographic study. To estimate proportions of muscarinic receptor subtypes variable wash times and displacement with pirenzepine were employed. [3H]Nicotine binding and total muscarinic binding in foetuses exceeded that in young adults by a factor of 6 and 2 respectively in the dentate nucleus, and by a factor of 3 in white matter. [3H]Nicotine and muscarinic binding was also higher in the foetal external granule cell layer than in the internal granule cell layer of adult, [125I]alpha-Bungarotoxin binding was raised in the dentate nucleus of the foetus compared with the adult. The M2 subtype appeared to be the predominant muscarinic receptor in the cerebellum, however it tended to represent a lower proportion of the muscarinic binding in the foetus than the adult. All 3 receptor types were highest in the foetal brainstem where the M3 + M4 muscarinic subtypes appeared to predominate. The p75 nerve growth factor receptor, measured by immunocytochemistry, in common with cholinergic receptors, paralleled choline acetyltransferase activity which has previously been reported to be high in the cerebellum during late foetal development and to fall in adulthood.

Acetylcholine↗

Body temperature effect on methylenedioxymethamphetamine-induced acute decrease in tryptophan hydroxylase activity.

Brain tryptophan hydroxylase activity decreases within 15 min after a single administration of 3,4-methylenedioxymethamphetamine. In the present study, the effect of body temperature on this acute decrease of tryptophan hydroxylase activity was examined. 2 h after a single dose of 3,4-methylenedioxymethamphetamine (20 mg/kg, s.c.), rats exhibited hyperthermia (38.7 degrees C) or hypothermia (35.8 degrees C) when maintained at 25 degrees C or 6 degrees C, respectively. The rectal temperature of control animals maintained at 6 degrees C was not altered. Tryptophan hydroxylase activity measured in the hippocampus, striatum and frontal cortex of hyperthermic rats treated with 3,4-methylenedioxymethamphetamine was decreased to 61%, 65%, and 71% of control levels, respectively, 2 h after drug treatment. However, in hypothermic rats, 3,4-methylenedioxymethamphetamine had no effect on tryptophan hydroxylase activity in the hippocampus, striatum or frontal cortex. Non-drug-induced hyperthermia or hypothermia did not affect tryptophan hydroxylase activity. Since hypothermia may prevent the 3,4-methylenedioxymethamphetamine-induced decrease in tryptophan hydroxylase activity by reducing the formation of free radicals, the effect of a free radical scavenging agent, N-tert-butyl-alpha-phenylnitrone, was examined. N-tert-butyl-alpha-phenylnitrone (200 mg/kg, i.p.) alone caused hypothermia but had no direct effect on tryptophan hydroxylase activity. Preadministration of N-tert-butyl-alpha-phenylnitrone prevented 3,4-methylenedioxymethamphetamine from raising the temperature above normal and attenuated the drug-induced decrease in tryptophan hydroxylase activity in hippocampus, striatum and frontal cortex. However, when the rats treated with a combination of N-tert-butyl-alpha-phenylnitrone and 3,4-methylenedioxymethamphetamine were maintained at hyperthermic conditions, N-tert-butyl-alpha-phenylnitrone had no protective effect. These results suggest that body temperature plays a prominent role in the 3,4-methylenedioxymethamphetamine-induced acute decrease in tryptophan hydroxylase activity.

Animals↗

Assessment of hibernating myocardium by dobutamine stimulation in a canine model.

OBJECTIVES: The purpose of this study was to 1) develop an animal model of hibernating myocardium, and 2) evaluate the ability of dobutamine stimulation to detect hibernating myocardium using both qualitative and quantitative assessment of regional myocardial function. BACKGROUND: Left ventricular dysfunction may be due to chronic ischemia with or without myocardial infarction and may improve after coronary blood flow is enhanced by revascularization procedures. This condition has been coined "hibernating myocardium" and variably defined in recent years. The results of recent clinical studies suggest that dobutamine echocardiography may be useful for detecting viable myocardium in patients with left ventricular dysfunction. METHODS: Twenty-one dogs underwent initial operation. Sonomicrometer crystals were implanted, and baseline measurements of segment shortening and wall thickening (by echocardiography) were made. A coronary artery was ligated; the chest was closed; and measurements were repeated. Dobutamine was incrementally infused with determination of wall thickening and segment shortening at baseline and on days 3 and 7 and weeks 2 and 4 after coronary artery occlusion. Finally, the chest was reopened; the ligated vessel was bypassed; and measurements were repeated. RESULTS: Of the 10 dogs that completed the entire protocol, 7 had varying degrees of nontransmural myocardial infarction (group 1), and 3 had complete transmural myocardial infarction (group 2). In group 1, baseline function was significantly impaired compared with preligation function but increased during dobutamine infusion. When reperfused after 4 weeks, both wall thickening and segment shortening increased significantly. In group 2, significant changes were not seen during the dobutamine studies or after reperfusion. Myocardial perfusion during dobutamine infusion increased in group 1 but did not change in group 2. CONCLUSIONS: We demonstrated improvement in chronically dysfunctional myocardium after restoration of previously interrupted myocardial blood flow in dogs after nontransmural myocardial infarction, thus validating a canine model of hibernating myocardium. As assessed by two independent methods, dobutamine infusion identified hibernating myocardium in an animal model.

Animals↗

Selective tumorigenesis in non-parenchymal liver epithelial cell lines by hepatocyte growth factor transfection.

Hepatocyte growth factor (HGF) has been recently suggested to contribute to tumorigenesis by an autocrine mechanism in fibroblast cells overexpressing its receptor, the MET/HGFR protein. Since epithelial cells represent the primary physiologic target of HGF, we investigated whether inappropriate expression of HGF by epithelial cells which normally express MET/HGFR may also contribute to tumorigenesis. We have transfected a full length rat HGF gene into three mouse epithelial cell lines, one derived from breast (MM55) and two (BNL CL.2 and NMuLi) representing liver non-parenchymal epithelial cells (NPEC). We confirmed the presence of the transfected gene by Southern blot analysis, the production of HGF protein by immunofluorescence, and the preservation of HGF biologic activity by bio-assay. In comparison to untransfected cells, all three HGF-transfected cell lines displayed high level MET/HGFR autophosphorylation and increased ability to proliferate in media containing low serum. The two HGF-transfected liver NPEC lines, but not the HGF-transfected mammary cell line, displayed loss of cell contact growth-inhibition and acquired a markedly increased ability to form colonies in soft agar. Furthermore, the NPEC HGF-transfected cell lines formed much larger tumors in nude mice than the untransfected counterparts, with extensive invasion and sporadic lung metastases. These results demonstrate that overexpression of HGF in at least some epithelial cells contribute to tumorigenesis, and furthermore suggest a possible role for the HGF-MET/HGFR system in the progression of certain epithelial tumors.

Animals↗

"Abnormal" illness behaviour in chronic fatigue syndrome and multiple sclerosis.

OBJECTIVE: To investigate the presence of abnormal illness behaviour in patients with a diagnosis of chronic fatigue syndrome. DESIGN: A cross sectional descriptive study using the illness behaviour questionnaire to compare illness behaviour scores and illness behaviour profiles of patients with chronic fatigue syndrome and patients with multiple sclerosis. SETTING: A multidisciplinary fatigue clinic and a teaching hospital neurology outpatient clinic. SUBJECTS: 98 patients satisfying the Oxford criteria for chronic fatigue syndrome and 78 patients with a diagnosis of multiple sclerosis. MAIN OUTCOME MEASURE: Responses to the 62 item illness behaviour questionnaire. RESULTS: 90 (92%) patients in the chronic fatigue syndrome group and 70 (90%) in the multiple sclerosis group completed the illness behaviour questionnaire. Both groups had significantly high scores on the general hypochondriasis and disease conviction subscales and significantly low scores on the psychological versus somatic concern subscale, as measured in relation to normative data. There were, however, no significant differences in the subscale scores between the two groups and the two groups had identical illness behaviour profiles. CONCLUSION: Scores on the illness behaviour questionnaire cannot be taken as evidence that chronic fatigue syndrome is a variety of abnormal illness behaviour, because the same profile occurs in multiple sclerosis. Neither can they be taken as evidence that chronic fatigue and multiple sclerosis share an aetiology. More needs to be known about the origins of illness beliefs in chronic fatigue syndrome, especially as they are important in determining outcome.

Adult↗

Salmeterol.

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Adrenergic beta-Agonists↗

Healing determinants in older people with leg ulcers.

A descriptive correlational design was used to identify the physiologic, therapeutic, and psychosocial determinants of leg ulcer healing in community-residing older people with venous and venous-arterial disease (N = 156). A regression model with healing rate as the dependent variable explained 49% of the variance. Increased pain when mobilizing, increased hours with limbs horizontal to the torso, and moderate and severe liposclerosis (hardening and induration of the skin) were associated with poorer healing rates. Higher wound status scores were associated with more rapid healing rates. Self-efficacy beliefs and social support were not significant factors. The findings suggest the need for early detection and management of limb pain that interferes with normal mobility. Limb position and edema assessment prior to the application of compression bandages is recommended, with bandages that provide clients with high compression when ambulant and low compression when resting being potentially beneficial.

Aged↗

The role of NMDA receptor systems in neuropeptide responses to stimulants of abuse.

High doses of stimulants of abuse, such as methamphetamine and cocaine, cause significant increases in the content of neurotension- and dynorphin-like immunoreactivity in the striatum and nucleus accumbens (approximately 200-600% of control) in the rat. These changes in neuropeptide content are caused by stimulation of dopamine D1 receptors and prevented by the glutamate NMDA receptor antagonist, MK 801. Stimulation of the NMDA receptor with N-methyl-D-aspartate results in increases in the neuropeptide levels like that caused by methamphetamine and cocaine. These findings demonstrate that stimulants of abuse profoundly influence neurotensin and dynorphin pathways associated with extrapyramidal and limbic structures by an interaction of activated dopamine D1 and glutamate NMDA receptors.

Animals↗

Osteogenic protein-1 induces dendritic growth in rat sympathetic neurons.

Sympathetic neurons from perinatal rat pups extend only a single axon when maintained in culture in the absence of glia and serum. Exposure to recombinant osteogenic protein-1 (OP-1) selectively induces the formation of dendrites that correctly segregate and modify cytoskeletal and membrane proteins and form synaptic contacts of appropriate polarity. OP-1 requires nerve growth factor (NGF) as a cofactor, and, in the presence of optimal concentrations of NGF, OP-1-induced dendritic growth from cultured perinatal neurons is comparable to that observed in situ. Sympathetic neuroblasts that had not formed dendrites in situ also responded to OP-1 in culture, indicating that OP-1 can cause de novo formation as well as regeneration of dendrites. These data imply that specific signals can regulate the development of neuronal shape and polarity.

Animals↗

Fluticasone propionate--an update on preclinical and clinical experience.

Fluticasone propionate (FP) is a novel androstane glucocorticoid with potent anti-inflammatory activity which has been effectively used, intranasally, as therapy for seasonal and allergic perennial rhinitis. When taken by the inhaled route, FP has shown significant therapeutic efficacy in the management of asthma. Fluticasone propionate is a highly lipophilic molecule with good uptake, binding and retention characteristics in human lung tissue. Fluticasone propionate has high glucocorticoid receptor selectivity and affinity, demonstrating rapid receptor association and slow receptor dissociation. In vitro, FP has been shown to potently inhibit T lymphocyte proliferation, cytokine generation, tumour necrosis factor alpha (TNF-alpha)-induced adhesion molecule expression, interleukin-5-induced eosinophilia, mucosal oedema and toluene 2,4-diisocyanate-induced mast cell proliferation, while promoting secretory leucocyte protease inhibitor production and eosinophil apoptosis. In human studies, FP has demonstrated marked vasoconstrictor potency in normal subjects and inhibited antigen-induced mucosal platelet activating factor/eicosanoid production, T lymphocytes and CD25+ cells in patients with rhinitis. Biopsy data from mild asthmatics demonstrate FP-associated reduction in CD3, CD4, CD8 and CD25 cells, with an accompanying reduction in eosinophil and mast cell markers. Clinical studies have evaluated lung function, bronchial reactivity, exacerbation rates and oral corticosteroid-sparing effect. Results show that FP has at least twice the clinical potency of beclomethasone dipropionate and budesonide. This appears to be achieved without an accompanying increase in systemic effects, suggesting a therapeutic index which may be higher than other currently available inhaled corticosteroids.

Androstadienes↗

A simple technique for fabrication of transmission block for concomitant treatment of bilateral anterior inguinal lymphatics and pelvic/perineal structures.

The efficacy of transmission block technique with contiguous photon irradiation of inguinal as well as pelvic and perineal structures has been reported in literature. In this paper, a simple and accurate method for the proper fabrication of transmission block has been described and also demonstrated to be effective and useful. The procedures for a precise geometrical alignment and dose verification are also detailed.

Anus Neoplasms↗

Effect of germanium-132 on galactose cataracts and glycation in rats.

Germanium compounds have been shown to be effective in preventing the formation of advanced glycation end-products and for reversible solubilization of glycated proteins. As protein glycation has been proposed to play a role in lens opacification, we initiated studies to evaluate the effects of 2-carboxyethyl germanium sesquioxide (germanium compound 132 or Ge-132) on galactose-induced cataractogenesis. For this study young Sprague-Dawley rats were fed a 50% galactose diet. One group of rats received topical saline and another group was administered Ge-132 in saline four times a day. The lenses were periodically examined with an ophthalmoscope and at desired intervals processed for light and scanning electron microscopy. Our observations, beginning at 3 days and continuing to 21 days of galactose feeding, exhibited the characteristic galactose-induced morphological alterations, which include the formation of vacuoles, cysts, membrane disruption and swelling of fibers and epithelial cells as well as disorganization of the bow in lenses of rats in both groups. However, in the majority of rats administered Ge-132 these alterations were delayed as compared to the lenses of rats administered saline. Our findings show that, although the initiation, progression and pattern of lens opacification in rats receiving saline and Ge-132 were similar, in the majority of lenses the progression and establishment of mature cataracts in the Ge-132 group of rats were delayed. Analysis of the water-soluble and water-insoluble lens-protein fractions for glycated proteins showed increased levels of the Amadori products and advanced glycation related fluorescent products in galactosemic rats treated with saline eye drops. In rats receiving the topical Ge-132 treatment the levels of these glycation products were substantially reduced to levels lower than control values. Prevention of glycation seems to be a mechanism by which cataract progression is delayed.

Animals↗